Results of the first phase 1 clinical trial of the HER-2/neupeptide (GP2) vaccine in disease-free breast cancer patients

摘要: BACKGROUND: HER-2/neu, overexpressed in breast cancer, is a source of immunogenic peptides that include GP2 and E75. Phase 2 testing E75 as an adjuvant vaccine has suggested clinical benefit. GP2, derived from the transmembrane portion HER-2/neu, differing binding characteristics may be more than Results first phase 1 trial peptide are presented. METHODS: Disease-free, lymph node-negative, human leukocyte antigen (HLA)-A2+ cancer patients were enrolled. This dose escalation included 4 groups to determine safety optimal peptide/granulocyte-macrophage colony-stimulating factor (GM-CSF) dose. Toxicities monitored. Immunologic response was assessed ex vivo via HLA-A2:immunoglobulin dimer assay detect GP2-specific CD8+ T cells (and E75-specific assess epitope spreading) delayed type hypersensitivity (DTH) reaction (medians/ranges). RESULTS: Eighteen All toxicities grade ≤2. Eight (88.9%) 9 3 required GM-CSF reductions for local reactions ≥100 mm or ≥2 systemic toxicity. reduced 125 μg final group. responded immunologically (GP2-specific prevaccination maximum, 0.4% [0.0%-2.0%] 1.1% [0.4%-3.6%], P < .001) (GP2 pre- postvaccination DTH, 0 [0.0-19.5 mm] 27.5 [0.0-114.5 mm, .001). also increased maximum (0.8% [0.0%-2.41%] 1.6% [0.86%-3.72%], .001). CONCLUSIONS: The appears safe well tolerated with minimal local/systemic elicited HER-2/neu–specific immune responses, including spreading, high-risk, node-negative patients. These findings support further investigation prevention recurrence. Cancer 2010. © 2010 American Society.